This invention relates to a method and apparatus for prenatal screening for fetal abnormalities.
The risk of many fetal abnormalities is known to be associated with advanced maternal age, and this factor has been used for many years as the basis for the selection of pregnant women at highest risk for further investigation. Further investigation involves the sampling of the amniotic fluid by amniocentesis in order to isolate fetal cells which may then be examined for chromosomal abnormalities by karyotyping. This is a procedure which is not completely free from risk to both mother and fetus. It is estimated that the risk of spontaneous miscarriage as a result of this procedure is of the order of 0.5% to 1.0%.
Other risk factors have been identified which may also be used in selecting those women at highest risk of fetal abnormality. For example Wald et al in European Patent No. 362294 B1 have described how maternal serum concentrations of alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG) and unconjugated estriol (UE3) taken in the second trimester of pregnancy (from 13 to 26 weeks) may be used to calculate an individual woman's risk of subsequently giving birth to a child with Down Syndrome. Macri in European Patent Specification No. 409956A has described how measurement of the free-beta subunit of hCG may also be used as a marker for fetal Down Syndrome. In our European Patent Specification No. 627032 we describe how the combination of the free beta hCG and pregnancy associated placental protein A (PAPP-A) may also be used to predict the risk of fetal abnormalities in the first trimester of pregnancy.
All maternal serum markers have been identified on the basis that the concentrations found in abnormal pregnancies differ from those in normal pregnancies. Current teaching dictates that substances found in maternal serum which do not show a difference in concentration between abnormal and normal pregnancies are not as useful as maternal serum markers. Some maternal serum markers are only of apparent use at certain stages of the pregnancy. For example PAPP-A concentrations are known to be lower in the first trimester of pregnancy where the fetus has Down Syndrome, yet show no difference in the second trimester of pregnancy. Conversely maternal serum hCG has been shown not to be a very effective marker for fetal Down Syndrome in the first trimester. Macintosh M.C.M & Chard T; Fetal. Mat. Med. Rev. 5 : 181-190, 1993--Wald N. J. Kennard A. & Smith D., Ann. Med., 26: 23-29, 1994. Current teaching therefore indicates that measurement of PAPP-A in the second trimester of pregnancy or hCG in the first trimester of pregnancy would be of no use in screening for fetal Down Syndrome.
It is desirable that methods of prenatal screening are developed in which a correction is possible to remove the influence of between subject variation.